Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators

Abstract

Active resolution of acute inflammation is a previously unrecognized interface between innate and adaptive immunity. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programmes that enable inflamed tissues to return to homeostasis. This Review presents new cellular and molecular mechanisms for the resolution of inflammation, revealing key roles for eicosanoids, such as lipoxins, and recently discovered families of endogenous chemical mediators, termed resolvins and protectins. These mediators have anti-inflammatory and pro-resolution properties, thereby protecting organs from collateral damage, stimulating the clearance of inflammatory debris and promoting mucosal antimicrobial defence.

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

“…Potential beneficial effects of EPA on atherosclerotic plaque include anti‐inflammatory and antioxidant effects, decreased adhesion of monocytes to the endothelium, decreased macrophage and foam cell accumulation in fatty streaks, and increased thickness of the fibrous cap overlying lipid‐rich plaque28, 29, 30 (reviewed in Nelson et al) 31. EPA and DHA are also converted to specialized proresolving lipid mediators, with EPA and DHA being the respective precursors of the E‐series and D‐series resolvins 32. The resolvins have been shown to stimulate the resolution of acute inflammation by stopping further neutrophil recruitment to inflamed tissues and stimulating nonphlogistic infiltration of monocytes, which differentiate into resolution macrophages 33.…”

“…These resolution macrophages then phagocytize and clear apoptotic neutrophils and debris, a process termed efferocytosis, which is a key step in resolution and prevention of chronic inflammation 33, 34. Recent research has shown that omega‐3 fatty acids may hasten the resolution of inflammation when converted to resolvins 32, 33. Formation of fibrous tissue is an end stage of the chronic inflammatory process with the recruitment of collagen to form a scar.…”

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

“…The 14S-HDHA produced by platelets or lymphocytes was likely transported to macrophages and there converted to 14S,21R-diHDHA through the transcellular biosynthesis mechanism for lipid mediators. 43,44 Macrophages are the main leukocytes in wounds at days 2 to 3 after wounding, when the wounds are still in the inflammation phase. 2 They are activated to phagocytose apoptotic PMNs, debris, and bacteria, and then coordinate later events of healing, including re-epithelialization, granulation tissue formation, and angiogenesis.…”

Pathophysiology of heart failure and frailty: a common inflammatory origin?

“…Importantly, the induction of inflammation leads to negative feedback pathways to resolve inflammation, via immune‐suppressive cytokines like IL‐10 or resolvins (Serhan et al ., 2008). These mediators enhance the clearance of dying neutrophils by macrophages, a process termed efferocytosis (Greenlee‐Wacker, 2016).…”